3-Nitrotyrosine inhibits fibroblast-mediated collagen gel contraction and chemotaxis

H. Sugiura, Xiang-de Liu, T. Ichikawa, M. Ichinose, S. I. Rennard

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Reactive nitrogen species induce tissue inflammation and nitrate tyrosine residues of various kinds of proteins. Recent studies have established that the free amino acid form of 3-nitrotyrosine induces cytotoxity and growth inhibition and alters the cellular function in cultured cells. The aim of this study was to evaluate whether 3-nitrotyrosine could affect tissue remodelling in fibroblasts. To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the fibroblast-mediated contraction of floating gels and chemotaxis towards fibronectin. In addition, the ability of fibroblasts to release fibronectin, transforming growth factor (TGF)-β1, fibronectin and vascular endothelial growth factor (VEGF) was assessed. 3-Nitrotyrosine significantly inhibited gel contraction (p<0.01) compared with control and this inhibition was abolished by nitric oxide synthase (NOS) inhibitor. 3-Nitrotyrosine did not affect TGF-β1 and VEGF but significantly decreased fibronectin release (p<0.01) into the media. 3-Nitrotyrosine significantly inhibited chemotaxis towards fibronectin through suppression of α5β1 integrin expression (p<0.01). NOS inhibitor also reversed 3-nitrotyrosine-inhibited chemotaxis (p<0.01). Finally, 3-nitrotyrosine enhanced the expression of the inducible type of NOS (p<0.01) and nitric oxide release (p<0.01) through nuclear factor-κB activation. These results suggest that the free amino acid form of 3-nitrotyrosine can affect the tissue repair process by modulating nitric oxide production. Copyright

Original languageEnglish (US)
Pages (from-to)1452-1460
Number of pages9
JournalEuropean Respiratory Journal
Volume34
Issue number6
DOIs
StatePublished - Dec 1 2009

Fingerprint

Chemotaxis
Collagen
Fibroblasts
Gels
Fibronectins
Transforming Growth Factors
Nitric Oxide Synthase
Vascular Endothelial Growth Factor A
Nitric Oxide
Reactive Nitrogen Species
Amino Acids
Aptitude
3-nitrotyrosine
Nitric Oxide Synthase Type II
Integrins
Nitrates
Tyrosine
Cultured Cells
Inflammation
Lung

Keywords

  • Inducible nitric oxide synthase
  • Nitric oxide
  • Reactive nitrogen species
  • Remodelling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

3-Nitrotyrosine inhibits fibroblast-mediated collagen gel contraction and chemotaxis. / Sugiura, H.; Liu, Xiang-de; Ichikawa, T.; Ichinose, M.; Rennard, S. I.

In: European Respiratory Journal, Vol. 34, No. 6, 01.12.2009, p. 1452-1460.

Research output: Contribution to journalArticle

Sugiura, H. ; Liu, Xiang-de ; Ichikawa, T. ; Ichinose, M. ; Rennard, S. I. / 3-Nitrotyrosine inhibits fibroblast-mediated collagen gel contraction and chemotaxis. In: European Respiratory Journal. 2009 ; Vol. 34, No. 6. pp. 1452-1460.
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